High purity filtration of aqueous media, such as in the fields of biotechnology, chemistry, electronics, pharmaceuticals, and the food and beverage industries requires the use of sophisticated filter modules that are not only capable of a high degree of separation, but that will tend to prevent contamination of the environment, of the medium to be filtered, and of the resulting filtrate. This is designed to prevent unwanted, often dangerous organisms, such as bacteria or viruses, as well as environmental contaminants, such as dust, dirt, and the like from entering into the process stream and end product. To ensure that the sterility and/or retention capability of the porous material responsible for the filtration is not compromised, integrity testing is a fundamental requirement of critical process filtration applications. For example, FDA guidelines recommend integrity testing of filter modules prior to use and after filtration. Typically this testing is initially performed after steam sterilization to ensure that the filter is not damaged; accordingly, care must be taken to ensure that sterility of the filter, and thus the filtrate, is not compromised. Post-processing, the filter integrity test is performed again in situ to detect whether the filter was compromised during use. This information can be used to alert operators to a potential problem immediately after processing, and to quickly take corrective action. Further, FDA guidelines require that integrity testing documentation be included with batch product records.
There are a variety of methods of integrity testing to detect the presence of oversized pores or defects that can compromise the retention capability of porous materials, including the particle challenge test, the liquid-liquid porometry test, the diffusion test, the bubble point test, the gas-liquid diffusion test and diffusion tests measuring tracer components. Some of these tests, such as the particle challenge test, are destructive and therefore cannot be used as a pre-use test. Gas-liquid diffusion tests often lack sensitivity for detecting small defects, due to the inherent background noise in these tests. Liquid-liquid porometry and bubble point tests are useful for ensuring that a membrane with the proper nominal pore size is installed, but lack sensitivity for identifying small numbers of small defects.
Also known in the art is the binary gas test, where two gases of differing permeabilities are driven through the liquid layer of a wetted filter. This test allows for improved defect detection sensitivity compared to the single gas diffusion test and other integrity tests. A sweep flow of the binary gas pair on the upstream side of the membrane to maintain a constant composition on the upstream (inlet) side of the filter is used. A pressure differential between the upstream and downstream side of the filter is established by elevating the pressure of the inlet gas. The concentration of the gases on the downstream (permeate) side of the filter (enriched in the faster permeating gas) is then measured, and this measured value is compared to a known expected value from an integral filter. A deviation from the expected value is indicative of a defect in the filter being tested.
The binary gas test typically uses CO2 and C2F6 as the binary gas pair and water as the wetting liquid. The use of CO2 is advantageous in that it is highly permeable in water, resulting in a high flow rate through the wetted filter and a rapid measurement of the permeate concentration. However, CO2 is costly, particularly in a binary gas mixture with the preferred gas pair C2F6. Furthermore, the use of this binary gas pair is undesirable in view of the greenhouse gas implications, since the permeate and sweep gases are emitted or must be captured to prevent emission to the ambient air.
Other binary gas pairs, such as O2 and N2, also have been used. This pair is convenient in that they are present in air, is low cost and is environmentally friendly. At room temperature, oxygen permeates through water about twice as fast as nitrogen. However, the permeability of oxygen in water is about 30 times slower than carbon dioxide, adding to the time necessary to complete the test in comparison to when CO2 is one of the binary gases.
The low permeate flow rate with air means that an extended time is required to flush the volume downstream of the filter and the volume up to and including the volume in the gas composition analyzer. Flushing is required to ensure that the measured composition is not compromised by mixing with any gas existing in the downstream volume prior to the start of the test. The long test time is in itself problematic but also introduces a secondary problem in that the liquid contained in the filter will tend to dry out due to liquid evaporation from both the upstream and downstream sides of the filter. If the pores dry out, the test can no longer be performed.
In light of the above, a need exists for an integrity test method for filters that allows for the use of relatively slow permeate gas pairs, but does not require excessive test times and minimizes or eliminates the risk that the filter will dry out during the test.